The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston, TX 77030, USA.
Cell Stem Cell. 2011 Jul 8;9(1):74-86. doi: 10.1016/j.stem.2011.05.017. Epub 2011 Jun 16.
Adipose stromal cells (ASCs) serve as mesenchymal progenitors in white adipose tissue (WAT). Intercellular interactions involving ASCs have remained obscure. By merging phage display technology with fluorescence-activated cell sorting (FACS), we screened a combinatorial library for peptides that target mouse ASCs in vivo. We isolated peptide CSWKYWFGEC that specifically homes to ASCs, used it as bait to purify the corresponding ASC surface receptor, and identified it as a previously unreported cleavage product of decorin (DCN) lacking the glycanation site (termed ΔDCN). We demonstrate that ΔDCN is differentially expressed on ASC surface. In a screen for ΔDCN-binding proteins, we identified resistin, an adipokine for which the receptor has been unknown. Expression of ΔDCN in 3T3-L1 cells promoted proliferation and migration but suppressed lipid accumulation upon adipogenesis induction, which was resistin dependent. We conclude that ΔDCN serves as a functional receptor of resistin in adipocyte progenitors and may regulate WAT expansion.
脂肪基质细胞(ASCs)作为白色脂肪组织(WAT)中的间充质祖细胞。涉及 ASCs 的细胞间相互作用仍不清楚。通过将噬菌体展示技术与荧光激活细胞分选(FACS)相结合,我们筛选了一个组合文库,以寻找在体内靶向小鼠 ASCs 的肽。我们分离出特异性归巢到 ASCs 的肽 CSWKYWFGEC,将其用作诱饵来纯化相应的 ASC 表面受体,并将其鉴定为缺乏糖基化位点的先前未报道的核心蛋白聚糖(DCN)的裂解产物(称为 ΔDCN)。我们证明 ΔDCN 在 ASC 表面上差异表达。在筛选 ΔDCN 结合蛋白时,我们鉴定出抵抗素,一种其受体未知的脂肪因子。在 3T3-L1 细胞中表达 ΔDCN 可促进增殖和迁移,但在诱导脂肪生成时抑制脂质积累,这依赖于抵抗素。我们的结论是,ΔDCN 作为脂肪细胞祖细胞中抵抗素的功能性受体,可能调节 WAT 的扩张。